New Study Urges Stronger Warning for Parkinson’s Medications Tied to Impulsive Behaviors

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Posted by  Rachel Dolhun, MD, October 24, 2014

New data supports more substantial warnings for dopamine agonists after confirming the strong association between these drugs and impulse control disorders (ICDs)— syndromes of compulsive gambling, hypersexuality and excessive shopping, to name a few.

This relationship has been known for many years but clinicians may have failed to grasp its magnitude and possible implications. A U.S. Food and Drug Administration (FDA) “black box” warning — a strong caution indicating a potentially serious medication side effect — would undoubtedly grab the attention of practitioners and change prescribing habits.

“The medical community does not appreciate how common these problems are and how serious they may be” says Howard D. Weiss, MD, director of the Parkinson’s Disease and Movement Disorder Programs at the LifeBridge Health Brain & Spine Institute in Baltimore. Dr. Weiss offered a commentary on the study.

Many Agonists Prescribed Despite Impulse Disorder Connection
Thomas Moore, AB, of the Institute for Safe Medicine Practices, and colleagues from Harvard Medical School and The University of Ottawa searched 10 years’ worth of submissions to the FDA Adverse Event Reporting System for reports of ICDs and correlated them with prescription medications.

Their findings, published in JAMA Internal Medicine, showed a significantly higher proportion of impulse control disorders with dopamine agonists as compared to other drugs. The majority of these agonists were prescribed for Parkinson’s disease but they also treat restless legs syndrome and hyperprolactinemia (a hormonal disorder). Pramipexole (Mirapex) and ropinirole (Requip) had the highest associations.  

Agonists bind to dopamine receptors in the brain, mimicking the chemical’s effect in regulating movement, risk-taking and reward-seeking. Pramipexole, ropinirole, and rotigotine (Neupro) are widely used to delay initiation of levodopa or lessen motor fluctuations. Apomorphine (Apokyn) is another dopamine agonist used as a rescue therapy for sudden “off” periods.

Impulse Disorders Can Gravely Impact Quality of Life
Impulse control disorders can take many forms — those mentioned earlier and also excessive eating, pathological hobbyism and taking higher than prescribed amounts of medication. The outcomes can range from a mere nuisance to disastrous consequences for family and social relationships, finances and careers. Dr. Weiss says he has personally witnessed people lose their homes because of bankruptcy related to gambling, divorce due to sexual misadventures, and seek hospitalization for depression stemming from impulsive actions.

No one is immune, but certain populations — younger males and anyone with a history of mood problems, obsessive-compulsive disorder, or prior drug or alcohol abuse — are at higher risk for these complications. People on dopamine agonists and their families need to be vigilant for odd behaviors. Clinicians must inquire specifically about buying lottery tickets and new interest in pornography rather than simply asking about general “side effects.” These conversations can be uncomfortable but are crucial to patient well-being.

Dr. Weiss encourages the medical field to accept that dopamine agonists are not necessarily safer or better than other medications. More than 2 million outpatient prescriptions for these drugs were dispensed in the United States in a single quarter in 2012. In their commentary, Dr. Weiss and his coauthor Gregory M. Pontone, MD, of Johns Hopkins University School of Medicine argue we have “overestimated the benefit and underestimated the risks associated with the use of dopamine receptor agonist drugs in patients with Parkinson’s disease.”

Bottom Line

• For people taking these medications, this knowledge should increase awareness of behaviors and attitudes. Dopamine agonists are effective in many people and not everyone will experience side effects. Any change to medications should of course be discussed with the prescriber.
• For physicians, this data can inform more thoughtful prescribing.
• For researchers, this information will reinforce continued investigation into more effective forms of available symptomatic therapies, like levodopa, and into curative therapies.

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